Potassium Carbonate → (3R,4R)-1-tert-butyl 3-ethyl 4-((R)-1-phenylethylamino)-piperidine-1,3-dicarboxylate

HRID 497443Notes

Reaction equation

HRID 497443 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[C@H:10]([NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[CH2:9][CH2:8][N:7]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6]1)=[O:4].[C:27](=O)([O-])[O-].[K+].[K+]>C(O)C>[CH2:1]([O:2][C:3]([C@H:5]1[C@H:10]([NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[CH2:9][CH2:8][N:7]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:6]1)=[O:4])[CH3:27]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 69748981(3S,4R)-4-[(R)-1-phenyl-ethylamino]-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

Product 1

HCID 11080151(3R,4R)-1-tert-butyl 3-ethyl 4-((R)-1-phenylethylamino)-piperidine-1,3-dicarboxylateYield 23%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a dry flask (3S,4R)-4-[(R)-1-phenyl-ethylamino]-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (13.78 g, 38.0 mmol) was dissolved in ethanol (400 mL) along with 3 Å molecular sieves (1.04 g). The mixture was heated to reflux over 2.5 hours. Potassium carbonate (26.3 g) was added and refluxing continued for 4 additional hours. The reaction mixture was cooled, filtered through a bed of celite, and concentrated in vacuo to give a crude oil (16.05 g). Purification by flash column chromatography (20-50% ethyl acetate/hexanes) provided a colorless oil (3.24 g, 23%). Unepimerized ethyl ester was also isolated (7.55 g, 53%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux over 2.5 hours
  3. temperaturerefluxing
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered through a bed of celite
  6. concentrationconcentrated in vacuo
  7. customto give a crude oil (16.05 g)
  8. customPurification by flash column chromatography (20-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2753ea3fc48d4a01987df7457127d2bb
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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